Expression of hypoxia inducible factor-1α and basic fibroblast factor in the tissues of colorectal adenocarcinoma

Objective To observe expression of hypoxia inducible factor-1α(HIF-1α)and basic fibroblast growth factor(BFGF)in the tissues of colorectal adenoearcinoma and analyze the relationship between expression of the two factors and biological behavior of colorectal adenocarcinoma.Methods The samples of colorectal adenocarcinoma(n=60)and para-adenocarcinoma(n=60)were taken from surgical resection patients and normal colorectal tissues (n=20) from patients with irritable bowel syndrome.The expression of HIF-1α and BFGF were detected by immunohistochemical staining (SP method).Results Positive rates of HIF-1αand BFGF in colorectal adenocarcinoma tissues were 61.7% and 65.0%,and positive rates of HIF-1α and BFGF in para-adenocarcinoma tissues were 10.0%and 13.3%(P<0.05,respectively);HIF-1αand BFGF were not detected in normal intestinal mucosa.There was no significant correlation with HIF-1α and BFGF expression in colorectal adenocarcinoma tissues to the sexuality,age,tumor size,tumorposition and differentiation(P>0.05).A significant correlation between expression of the two factors and Dukes stage was observed (P<0.05).Positive rates of HIF-1α and BFGF in colorectal adenocarcinoma tissuesof Dukes A and B stage were 47.2%and 52.7%,respectively.Positive rates of HIF-1α and BFGF in colorectal adenocarcinoma tissues of Dukes C and D stage were 83.3%and 83.3%.respectively.There was a positive correlation between expression of the two factors and carcinogenesis of colorectal adenocarcinoma(r=0.4276.P<0.001).Conclusion The results showed that the enhanced expression of HIF-1 α and BFGF incolorectal adenocarcinoma tissues may be associated with the prognosis of the patients with colorectal adenocarcinoma,and HIF-1α and BFGF may participate synergistically in the carcinogenesis of colorectal adenocarcinoma.     

Expression of hypoxia inducible factor-1α and basic fibroblast factor in the tissues of colorectal adenocarcinoma

Objective To observe expression of hypoxia inducible factor-1α(HIF-1α)and basic fibroblast growth factor(BFGF)in the tissues of colorectal adenoearcinoma and analyze the relationship between expression of the two factors and biological behavior of colorectal adenocarcinoma.Methods The samples of colorectal adenocarcinoma(n=60)and para-adenocarcinoma(n=60)were taken from surgical resection patients and normal colorectal tissues (n=20) from patients with irritable bowel syndrome.The expression of HIF-1α and BFGF were detected by immunohistochemical staining (SP method).Results Positive rates of HIF-1αand BFGF in colorectal adenocarcinoma tissues were 61.7% and 65.0%,and positive rates of HIF-1α and BFGF in para-adenocarcinoma tissues were 10.0%and 13.3%(P<0.05,respectively);HIF-1αand BFGF were not detected in normal intestinal mucosa.There was no significant correlation with HIF-1α and BFGF expression in colorectal adenocarcinoma tissues to the sexuality,age,tumor size,tumorposition and differentiation(P>0.05).A significant correlation between expression of the two factors and Dukes stage was observed (P<0.05).Positive rates of HIF-1α and BFGF in colorectal adenocarcinoma tissuesof Dukes A and B stage were 47.2%and 52.7%,respectively.Positive rates of HIF-1α and BFGF in colorectal adenocarcinoma tissues of Dukes C and D stage were 83.3%and 83.3%.respectively.There was a positive correlation between expression of the two factors and carcinogenesis of colorectal adenocarcinoma(r=0.4276.P<0.001).Conclusion The results showed that the enhanced expression of HIF-1 α and BFGF incolorectal adenocarcinoma tissues may be associated with the prognosis of the patients with colorectal adenocarcinoma,and HIF-1α and BFGF may participate synergistically in the carcinogenesis of colorectal adenocarcinoma.     

Expression of hypoxia inducible factor-1α and basic fibroblast factor in the tissues of colorectal adenocarcinoma

Objective To observe expression of hypoxia inducible factor-1α(HIF-1α)and basic fibroblast growth factor(BFGF)in the tissues of colorectal adenoearcinoma and analyze the relationship between expression of the two factors and biological behavior of colorectal adenocarcinoma.Methods The samples of colorectal adenocarcinoma(n=60)and para-adenocarcinoma(n=60)were taken from surgical resection patients and normal colorectal tissues (n=20) from patients with irritable bowel syndrome.The expression of HIF-1α and BFGF were detected by immunohistochemical staining (SP method).Results Positive rates of HIF-1αand BFGF in colorectal adenocarcinoma tissues were 61.7% and 65.0%,and positive rates of HIF-1α and BFGF in para-adenocarcinoma tissues were 10.0%and 13.3%(P<0.05,respectively);HIF-1αand BFGF were not detected in normal intestinal mucosa.There was no significant correlation with HIF-1α and BFGF expression in colorectal adenocarcinoma tissues to the sexuality,age,tumor size,tumorposition and differentiation(P>0.05).A significant correlation between expression of the two factors and Dukes stage was observed (P<0.05).Positive rates of HIF-1α and BFGF in colorectal adenocarcinoma tissuesof Dukes A and B stage were 47.2%and 52.7%,respectively.Positive rates of HIF-1α and BFGF in colorectal adenocarcinoma tissues of Dukes C and D stage were 83.3%and 83.3%.respectively.There was a positive correlation between expression of the two factors and carcinogenesis of colorectal adenocarcinoma(r=0.4276.P<0.001).Conclusion The results showed that the enhanced expression of HIF-1 α and BFGF incolorectal adenocarcinoma tissues may be associated with the prognosis of the patients with colorectal adenocarcinoma,and HIF-1α and BFGF may participate synergistically in the carcinogenesis of colorectal adenocarcinoma.     

Effect of PKC signalling pathway and aldose reductase on expression of fibronectin induced by transforming growth factor-β1 in human mesangial cells

Objective To study the effect of PKC signalling pathway and aldose reductase (AR) on the expression of fibronectin (FN) induced by transforming growth factor-β1 (TGF-β1). Methods Human mesangial cells (HMCs) were cultured and transfected with pcDNA3-AR, and subject to AR gene silencing with small interfering RNA (siRNA) and then the cell was treated with recombinant human TGF-β1. The AR mRNA expression in the HMCs was examined using real time RT-PCR and protein expression of AR and FN was detected by Western blotting. Results The cultured HMC treated with TGF-$l showed increased expression of AR and FN,the normal HMC showed not reduced expression of FN after incubation with single inhibitors of AR. Pre-incubation of cells with inhibitors of AR and PKC, then the different groups of cells were treated with TGF-$l ,and the induction effect on FN expression was suppressed (34%) in HMC. HMCs transfected with AR showed a strong protein expression of FN, which was increased by 3. 6-fold after treatment with TGF-pl (P <0. 05) , and the induction effect on FN expression was suppressed by G(O)6983 (42%) in HMCs (P < 0. 05) . The HMC with AR gene knock-down by siRNA showed a decreased expression of AR and 90% decrease of FN protein in HMCs(P <0. 01) , and TGF-β1-induced up-regulation of FN was significantly suppressed by siRNA (12%) in HMCs (P <0. 01). Conclusions AR is capable of regulating FN expression only in the presence of TGF-β1, and this reaction is possibly accomplished through the activation of PKC signalling pathway.     

Effect of PKC signalling pathway and aldose reductase on expression of fibronectin induced by transforming growth factor-β1 in human mesangial cells

Objective To study the effect of PKC signalling pathway and aldose reductase (AR) on the expression of fibronectin (FN) induced by transforming growth factor-β1 (TGF-β1). Methods Human mesangial cells (HMCs) were cultured and transfected with pcDNA3-AR, and subject to AR gene silencing with small interfering RNA (siRNA) and then the cell was treated with recombinant human TGF-β1. The AR mRNA expression in the HMCs was examined using real time RT-PCR and protein expression of AR and FN was detected by Western blotting. Results The cultured HMC treated with TGF-$l showed increased expression of AR and FN,the normal HMC showed not reduced expression of FN after incubation with single inhibitors of AR. Pre-incubation of cells with inhibitors of AR and PKC, then the different groups of cells were treated with TGF-$l ,and the induction effect on FN expression was suppressed (34%) in HMC. HMCs transfected with AR showed a strong protein expression of FN, which was increased by 3. 6-fold after treatment with TGF-pl (P <0. 05) , and the induction effect on FN expression was suppressed by G(O)6983 (42%) in HMCs (P < 0. 05) . The HMC with AR gene knock-down by siRNA showed a decreased expression of AR and 90% decrease of FN protein in HMCs(P <0. 01) , and TGF-β1-induced up-regulation of FN was significantly suppressed by siRNA (12%) in HMCs (P <0. 01). Conclusions AR is capable of regulating FN expression only in the presence of TGF-β1, and this reaction is possibly accomplished through the activation of PKC signalling pathway.     

Expression of hypoxia inducible factor-1α and basic fibroblast factor in the tissues of colorectal adenocarcinoma

Objective To observe expression of hypoxia inducible factor-1α(HIF-1α)and basic fibroblast growth factor(BFGF)in the tissues of colorectal adenoearcinoma and analyze the relationship between expression of the two factors and biological behavior of colorectal adenocarcinoma.Methods The samples of colorectal adenocarcinoma(n=60)and para-adenocarcinoma(n=60)were taken from surgical resection patients and normal colorectal tissues (n=20) from patients with irritable bowel syndrome.The expression of HIF-1α and BFGF were detected by immunohistochemical staining (SP method).Results Positive rates of HIF-1αand BFGF in colorectal adenocarcinoma tissues were 61.7% and 65.0%,and positive rates of HIF-1α and BFGF in para-adenocarcinoma tissues were 10.0%and 13.3%(P<0.05,respectively);HIF-1αand BFGF were not detected in normal intestinal mucosa.There was no significant correlation with HIF-1α and BFGF expression in colorectal adenocarcinoma tissues to the sexuality,age,tumor size,tumorposition and differentiation(P>0.05).A significant correlation between expression of the two factors and Dukes stage was observed (P<0.05).Positive rates of HIF-1α and BFGF in colorectal adenocarcinoma tissuesof Dukes A and B stage were 47.2%and 52.7%,respectively.Positive rates of HIF-1α and BFGF in colorectal adenocarcinoma tissues of Dukes C and D stage were 83.3%and 83.3%.respectively.There was a positive correlation between expression of the two factors and carcinogenesis of colorectal adenocarcinoma(r=0.4276.P<0.001).Conclusion The results showed that the enhanced expression of HIF-1 α and BFGF incolorectal adenocarcinoma tissues may be associated with the prognosis of the patients with colorectal adenocarcinoma,and HIF-1α and BFGF may participate synergistically in the carcinogenesis of colorectal adenocarcinoma.     

Expression of hypoxia inducible factor-1α and basic fibroblast factor in the tissues of colorectal adenocarcinoma

Objective To observe expression of hypoxia inducible factor-1α(HIF-1α)and basic fibroblast growth factor(BFGF)in the tissues of colorectal adenoearcinoma and analyze the relationship between expression of the two factors and biological behavior of colorectal adenocarcinoma.Methods The samples of colorectal adenocarcinoma(n=60)and para-adenocarcinoma(n=60)were taken from surgical resection patients and normal colorectal tissues (n=20) from patients with irritable bowel syndrome.The expression of HIF-1α and BFGF were detected by immunohistochemical staining (SP method).Results Positive rates of HIF-1αand BFGF in colorectal adenocarcinoma tissues were 61.7% and 65.0%,and positive rates of HIF-1α and BFGF in para-adenocarcinoma tissues were 10.0%and 13.3%(P<0.05,respectively);HIF-1αand BFGF were not detected in normal intestinal mucosa.There was no significant correlation with HIF-1α and BFGF expression in colorectal adenocarcinoma tissues to the sexuality,age,tumor size,tumorposition and differentiation(P>0.05).A significant correlation between expression of the two factors and Dukes stage was observed (P<0.05).Positive rates of HIF-1α and BFGF in colorectal adenocarcinoma tissuesof Dukes A and B stage were 47.2%and 52.7%,respectively.Positive rates of HIF-1α and BFGF in colorectal adenocarcinoma tissues of Dukes C and D stage were 83.3%and 83.3%.respectively.There was a positive correlation between expression of the two factors and carcinogenesis of colorectal adenocarcinoma(r=0.4276.P<0.001).Conclusion The results showed that the enhanced expression of HIF-1 α and BFGF incolorectal adenocarcinoma tissues may be associated with the prognosis of the patients with colorectal adenocarcinoma,and HIF-1α and BFGF may participate synergistically in the carcinogenesis of colorectal adenocarcinoma.     

Expression of hypoxia inducible factor-1α and basic fibroblast factor in the tissues of colorectal adenocarcinoma

Objective To observe expression of hypoxia inducible factor-1α(HIF-1α)and basic fibroblast growth factor(BFGF)in the tissues of colorectal adenoearcinoma and analyze the relationship between expression of the two factors and biological behavior of colorectal adenocarcinoma.Methods The samples of colorectal adenocarcinoma(n=60)and para-adenocarcinoma(n=60)were taken from surgical resection patients and normal colorectal tissues (n=20) from patients with irritable bowel syndrome.The expression of HIF-1α and BFGF were detected by immunohistochemical staining (SP method).Results Positive rates of HIF-1αand BFGF in colorectal adenocarcinoma tissues were 61.7% and 65.0%,and positive rates of HIF-1α and BFGF in para-adenocarcinoma tissues were 10.0%and 13.3%(P<0.05,respectively);HIF-1αand BFGF were not detected in normal intestinal mucosa.There was no significant correlation with HIF-1α and BFGF expression in colorectal adenocarcinoma tissues to the sexuality,age,tumor size,tumorposition and differentiation(P>0.05).A significant correlation between expression of the two factors and Dukes stage was observed (P<0.05).Positive rates of HIF-1α and BFGF in colorectal adenocarcinoma tissuesof Dukes A and B stage were 47.2%and 52.7%,respectively.Positive rates of HIF-1α and BFGF in colorectal adenocarcinoma tissues of Dukes C and D stage were 83.3%and 83.3%.respectively.There was a positive correlation between expression of the two factors and carcinogenesis of colorectal adenocarcinoma(r=0.4276.P<0.001).Conclusion The results showed that the enhanced expression of HIF-1 α and BFGF incolorectal adenocarcinoma tissues may be associated with the prognosis of the patients with colorectal adenocarcinoma,and HIF-1α and BFGF may participate synergistically in the carcinogenesis of colorectal adenocarcinoma.     

Expression of hypoxia inducible factor-1α and basic fibroblast factor in the tissues of colorectal adenocarcinoma

Objective To observe expression of hypoxia inducible factor-1α(HIF-1α)and basic fibroblast growth factor(BFGF)in the tissues of colorectal adenoearcinoma and analyze the relationship between expression of the two factors and biological behavior of colorectal adenocarcinoma.Methods The samples of colorectal adenocarcinoma(n=60)and para-adenocarcinoma(n=60)were taken from surgical resection patients and normal colorectal tissues (n=20) from patients with irritable bowel syndrome.The expression of HIF-1α and BFGF were detected by immunohistochemical staining (SP method).Results Positive rates of HIF-1αand BFGF in colorectal adenocarcinoma tissues were 61.7% and 65.0%,and positive rates of HIF-1α and BFGF in para-adenocarcinoma tissues were 10.0%and 13.3%(P<0.05,respectively);HIF-1αand BFGF were not detected in normal intestinal mucosa.There was no significant correlation with HIF-1α and BFGF expression in colorectal adenocarcinoma tissues to the sexuality,age,tumor size,tumorposition and differentiation(P>0.05).A significant correlation between expression of the two factors and Dukes stage was observed (P<0.05).Positive rates of HIF-1α and BFGF in colorectal adenocarcinoma tissuesof Dukes A and B stage were 47.2%and 52.7%,respectively.Positive rates of HIF-1α and BFGF in colorectal adenocarcinoma tissues of Dukes C and D stage were 83.3%and 83.3%.respectively.There was a positive correlation between expression of the two factors and carcinogenesis of colorectal adenocarcinoma(r=0.4276.P<0.001).Conclusion The results showed that the enhanced expression of HIF-1 α and BFGF incolorectal adenocarcinoma tissues may be associated with the prognosis of the patients with colorectal adenocarcinoma,and HIF-1α and BFGF may participate synergistically in the carcinogenesis of colorectal adenocarcinoma.     

Expression of hypoxia inducible factor-1α and basic fibroblast factor in the tissues of colorectal adenocarcinoma

Objective To observe expression of hypoxia inducible factor-1α(HIF-1α)and basic fibroblast growth factor(BFGF)in the tissues of colorectal adenoearcinoma and analyze the relationship between expression of the two factors and biological behavior of colorectal adenocarcinoma.Methods The samples of colorectal adenocarcinoma(n=60)and para-adenocarcinoma(n=60)were taken from surgical resection patients and normal colorectal tissues (n=20) from patients with irritable bowel syndrome.The expression of HIF-1α and BFGF were detected by immunohistochemical staining (SP method).Results Positive rates of HIF-1αand BFGF in colorectal adenocarcinoma tissues were 61.7% and 65.0%,and positive rates of HIF-1α and BFGF in para-adenocarcinoma tissues were 10.0%and 13.3%(P<0.05,respectively);HIF-1αand BFGF were not detected in normal intestinal mucosa.There was no significant correlation with HIF-1α and BFGF expression in colorectal adenocarcinoma tissues to the sexuality,age,tumor size,tumorposition and differentiation(P>0.05).A significant correlation between expression of the two factors and Dukes stage was observed (P<0.05).Positive rates of HIF-1α and BFGF in colorectal adenocarcinoma tissuesof Dukes A and B stage were 47.2%and 52.7%,respectively.Positive rates of HIF-1α and BFGF in colorectal adenocarcinoma tissues of Dukes C and D stage were 83.3%and 83.3%.respectively.There was a positive correlation between expression of the two factors and carcinogenesis of colorectal adenocarcinoma(r=0.4276.P<0.001).Conclusion The results showed that the enhanced expression of HIF-1 α and BFGF incolorectal adenocarcinoma tissues may be associated with the prognosis of the patients with colorectal adenocarcinoma,and HIF-1α and BFGF may participate synergistically in the carcinogenesis of colorectal adenocarcinoma.     

Differential induction of Egr-1 expression in WEHI-231 sublines does not correlate with apoptosis

To determine whether the absence of inducible Egr-1 expression correlates with apoptosis and growth arrest, we compared the inducible expression of two Egr family members (Egr-1 and Egr-2) in three sublines WEHI-231. Expression of Egr-2 is induced in all sublines of WEHI-231 following surface immunoglobulin (sIg) cross-linking, but Egr-1 expression is induced in only two. We find that the lack of inducible Egr-1 expression corresponded to an increase in the methylation pattern of the Egr-1 gene. In spite of these differences in Egr-1 expression, all the sublines demonstrate similar inhibition of [³H] thymidine incorporation following anti-Ig treatment. Growth arrest leads to apoptosis in only two of the sublines, but apoptosis does not correlate with the absence of inducible Egr-1 expression. Demethylation, by treatment with 5-azacytidine, in the Egr-1 non-expressing subline allows for induction of Egr-1 expression by anti-Ig, but fails to prevent growth arrest and apoptosis. Therefore, we conclude that the lack of Egr-1 expression is not responsible for either the apoptotic response or growth arrest induced by anti-Ig in WEHI-231.     

二氧化硅活化巨噬细胞中核转录因子早期生长反应基因-1的表达

目的 研究二氧化硅(SiO2)刺激的巨噬细胞中核转录因子早期生长反应基因-1(early growth response gene-1,Egr-1)表达和定位分布的动态变化,探讨Egr-1在硅沉着病发病机制中的作用。方法 用免疫组织化学方法观察大鼠实验性硅沉着病组织中肺巨噬细胞Egr-1表达的动态变化;用逆转录-聚合酶链反应(RT—PCR)、Western印迹和免疫荧光方法分别检测体外SiO2刺激的巨噬细胞系RAW264．7中Egr-1 mRNA、蛋白表达及其定位。结果 大鼠实验性硅沉着病中肺巨噬细胞Egr-1表达明显上调,阳性反应强度在14d时达到高峰。体外SiO2作用RAW264．7细胞15～240min,Egr-1 mRNA表达均明显增高,峰值位于15min,480min时仅微量表达。Egr-1蛋白于60min时核移位最明显,持续至120min,随后减少;在60～120min时间内,Egr-1核蛋白及总蛋白的表达量亦达峰值,其后开始下降。结论 SiO2能激活巨噬细胞中核转录因子Egr-1,提示Egr-1可能在硅沉着病的发生发展中起重要的调控作用。     

人肝癌及相关组织中Egr—1基因的转录表达及其意义

目的：探讨Egr-1在肝癌癌变过程中的作用。方法：采用原位杂交和免疫组化技术,检测了肝癌及相关组织中Egr-1的mRNA转录水平和蛋白表达,以人乳腺和小鼠肝及大脑组织为对照。结果：在肝癌组织和正常肝组织中,Egr-1的转录水平明显减低或无转录信号;癌旁组织如肝癌癌旁的异型增生（LCD）和“萎缩样肝索”中Egr-1的转录水平明显增高。Egr-1基因在肝癌组织的表达与mRNA检测结果基本一致。在乳腺及小鼠脑组织Egr-1的表达明显增高。结论：Egr-1在肝癌中的缺失表达可能在其癌变过程中正常生长失调方面起作用;Egr-1在正常肝、乳腺及细胞中的表达差异可能与这些细胞的增殖、分化状态及细胞类型特异性有关。     

流体剪切力调节内皮细胞组织因子表达的初步探讨

目的探讨流体剪切力调节内皮细胞组织因子(tissue factor,TF)表达的机制。方法将脐静脉内皮细胞置于平行板流动腔中接受1．2 Pa(1 dyn／cm2=0．1 Pa)剪切力作用20 min后,采用凝胶电泳迁移率改变法(electorohoretic mobility shift analysis,EMSA)和蛋白免疫印迹分析(Western Blot,WB)检测转录因子Egr-1和Sp1在TF基因表达过程中的表达情况。结果 (1)静止组可见Sp1表达而无Egr-1表达;(2)剪切力组Sp1磷酸化水平和Egr-1表达水平均明显增高;(3)EMSA显示,对于Sp1／Egr-1结合位点,Egr-1对Sp1具有较强的竞争抑制作用。结论流体剪切力调节TF基因表达过程中,不同转录因子起着不同的作用:Sp1主要维持内皮细胞TF基因的基础表达;Egr-1竞争靶位点上的Sp1和磷酸化Sp1可能共同参与流体剪切力诱导TF基因表达。     

组胺对星形胶质细胞Egr-1表达的调节作用

 目的: 探讨组胺对星形胶质细胞早期反应生长因子-1(Egr-1)表达是否具有调节作用。方法: 将野生型(WT)和组氨酸脱羧酶敲除(HDC-KO)小鼠及组胺处理的HDC-KO小鼠取脑,并提取皮层组织总RNA。将原代培养的大鼠皮层星形胶质细胞分别给予不同浓度的组胺(10^-8、10^-7、10^-6、10^-5或10^-4 mol/L)处理15、30、60、120或240 min。组胺H₁、H₂受体拮抗剂分别于组胺给药前15 min加入。组胺处理完毕后,提取细胞总RNA或蛋白。利用real-time PCR和Western blot测定Egr-1的表达。结果: 与WT小鼠相比,HDC-KO小鼠大脑皮层Egr-1的mRNA表达量显著降低,而外源性给予组胺则能促进其Egr-1的mRNA表达。在培养的星形胶质细胞上,组胺可促进Egr-1的mRNA表达,其中10^-5 mol/L的组胺作用最强,而组胺(10^-5 mol/L)处理30 min时Egr-1的mRNA表达量达到峰值,相应的Egr-1蛋白表达于60 min时显著增高,该作用可被组胺H₁受体拮抗剂而非H₂受体拮抗剂显著抑制。结论: 组胺对大脑皮层组织及培养的星形胶质细胞Egr-1表达具有上调作用,该作用与激动组胺H₁受体有关。